The HOS cell line, which was originally derived from a human osteosarcoma, is non-tumorigenic and can be transformed to anchorage-independent growth and tumor igenicity by N-methyl-N'-nitro-N-Nitrosoguanidine (MNNG) or 7,12 dimethylbenz(a)-anthracene (DMBA). It was shown previously that DNA prepared from the MNNG-HOS, transformed cell line will transform NIH 3T3 cells in DNA transfection assays, whereas DNA prepared from either HOS cells or DMBA-HOS cells failed to induce foci. The MNNG-HOS transforming gene (met), which has been cloned in several overlapping lambda clones, totaling 40 kb of the human sequence, shows no homology with the known members of the ras oncogene family nor with the viral oncogenes mos, myc, myb, src, erb, sis, rel or with the B-lym gene. There has been no rearrangement of met gene sequences within MNNG-HOS cells when compared with HOS cell DNA, human placental DNA or DNA from several human tumors. Cloned probes specific for the met gene detect a major species of polyadenylated RNA isolated from MNNG-HOS NIH 3T3 transformants. Using somatic cell hybrids, the human met transforming gene has been mapped to chromosome 7.